A phospholipid spin label used as a liposome-associated MRI contrast agent

Given current clinical use of phospholipid bilayer structures (liposomes/vesicles) as nontoxic drug delivery vehicles, we have addressed the possibility of employing the phospholipids themselves as MRI contrast agents. To this end we have synthesized phosphatidylcholine with a nitroxide spin label replacing one methyl residue of the choline headgroup. This material was mixed with natural phosphatidylcholine in mole ratios from 1:50 to 1:1 and used to prepare sonicated unilamellar vesicles in saline. Expected structural features of these vesicles were verified by freeze-fracture electron microscopy. Proton T1 values of saline were readily decreased to less than 0.3 s by such preparations, yielding a net relaxivity of 0.6 M-1 s-1. The approach seems to be a realistic way of firmly associating a contrast agent of minimal toxicity with ordinary liposomes/vesicles in a manner that is not subject to leakage.     

Family History of Alcoholism Does Not Predict Neuropsychological Performance in Alcoholics

We examined the relationship of history of alcoholism in first-degree relatives to neuropsychological performance of alcoholics abstinent from several weeks to several years. Eighty-four men were assigned to four groups based on "strength" of family history of alcoholism. The groups were: (1) "strong history," a parent plus another first-degree relative positive; (2) "moderate," parent only positive; (3) "weak," nonparent first-degree relative only positive; and (4) "negative," no first-degree relative positive. There were no significant between-group differences in NP performance. In other analyses there were no NP differences between alcoholics classified positive or negative purely on basis of paternal alcoholism, and no differences between subjects who had multigenerational versus unigenerational versus negative familial histories of alcoholism. It is concluded that genetic loading for alcoholism does not significantly affect the NP status of abstinent alcoholic groups equated for education, drinking history, and medical risk.     

Is Electric Arc Welding Linked to Manganism or Parkinson’s Disease?

Manganese and its inorganic compounds are widely used in many industries and have been accepted as occupational neurotoxins that have caused a distinct and disabling clinical entity, manganism, in several types of work, notably where exposure is by way of dust. There is inconclusive and inconsistent evidence that, in these occupations, subclinical neurological effects, detectable only by neurobehavioural studies, may be caused by low doses. This has prompted a re-evaluation of occupational exposure limits. Some countries, including the UK, already demand much higher levels of protection against exposure than 5 years ago. Welding is the most common source of occupational exposure as manganese is an essential component of steel and so its compounds are inevitable components of fume emitted from steel welding processes. There it is found in respirable particles, often as complex oxides (spinels), sometimes within a core protected by a silicon oxide shell — as distinct from the much simpler form of particle formed by disintegration in processes such as mining and ore milling where manganism has been diagnosed convincingly. Millions of workers are at risk of exposure to manganese-containing compounds in fumes from electric arc welding of steel. In recent years it has been asserted that neurological and neurobehavioural disorders may develop consequent to exposure to steel welding fumes and that employment as a welder is associated with the unusually early onset of Parkinson’s disease. Causal relationships have been postulated. Welders have been recorded as having been exposed to high levels of manganese-containing fume, especially where they have worked in confined, unventilated spaces, although this appears from limited data to be the exception rather than the rule. Even then the dose received is generally less than in mining or ore crushing. When care is taken to exclude exposures from hardfacing and burning and cutting arc processes, where manganese may form a high percentage of the fume, manganese compounds usually form a relatively low percentage of the composition of welding fume particles, <2.0%, much outweighed by iron. Although these manganese-compound-containing welding fume particles are insoluble in water, the manganese compounds in particles that are retained in the alveoli may be absorbed, at least in part. Manganese concentrations in biological material samples in some exposed groups reflect this relative to unexposed workers. Some of the transfer systems for absorption and transport, including across the blood-brain barrier, are used in competition with iron which is present in abundance in welding fume. This may reduce absorption of manganese in welders and thus reduce the opportunity for sufficient doses to cause neurotoxicological consequences. Scrutiny of the literature covering the last 40 years has revealed only five cases that meet sufficient criteria for manganism to just cross the diagnostic threshold, and even then they carry a degree of doubt with them. This low incidence alone gives notice that welders have not been and are not at high risk of clinically apparent damage from exposure to manganese. If this needs to be further emphasised, there is the fact that the literature contains no confirmed cases of manganism in welders. Assertions of abnormal results in neurobehavioural studies of welders have raised the possibility of there being a subclinical form of manganism with loss of fine motor control as one of its features. While observations of such changes in workers in other industries have caused regulators in some countries to apply more stringent controls of exposure, as yet the results lack convincing consistency and there is no indication of any dose-effect relationship. If welding fume can have these motor effects it would be a heavy and perhaps career-ending blow to those affected. It would not be prudent to dismiss the warnings sounded by the results of studies of welders, no matter how flawed these investigations are, but wiser and better to act with vigour to reduce exposure and monitor the effectiveness of this additional protection whilst conducting high quality research to allow sound conclusions to be drawn as to whether there actually is a subclinical disorder. Idiopathic Parkinson’s disease is a common disorder affecting 1–2% of those in the general population aged >65 years. It has been suggested, on flawed and contested evidence, not that welding causes the disease but rather that employment as a welder carries with it the risk of developing this disease at a younger age than if that trade had not been followed. Manganese in welding fume has been nominated as the neurotoxin. This may be biologically feasible if manganese destroys insufficient receptor cells to produce clinical manganism but sufficient to enhance the effects of a reduced supply of dopamine to give the manifestations of already developing idiopathic Parkinson’s disease earlier in the course of destruction of the substantia nigra than if all receptors were intact.     

Use of triple-lumen subclavian catheters for administration of total parenteral nutrition.

This study evaluated the safety of triple vs single-lumen catheters in intravenous nutrition. Patients who were judged likely to benefit from a triple-lumen catheter were randomized to receive either a single-lumen catheter, with additional peripheral or central venous access as needed, or a triple-lumen catheter. All patients were at increased risk of catheter-related infection because of one or more of the following conditions: > 60 years of age, breakdown of skin integrity, severe underlying illness, diagnosis of acute pancreatitis, recent head or neck surgery, or presence of a preexisting infection. Patients were excluded who had neutropenia, were immunosuppressed, had body burns > 40%, or had contaminated wounds in the subclavicular area. Of 204 patients entered between June 1989 and November 1991, 177 completed the required > or = 7 days of therapy. Seventy-eight of these patients were randomized to a single-lumen catheter and 99 to a triple-lumen catheter. Catheters were inserted and maintained by the Nutrition Support Team. Dressings were monitored daily and changed weekly using a bio-occlusive dressing. When parameters were met for a possible septic episode, simultaneous peripheral and central catheter blood cultures were obtained using the Isolator method. Catheter-related sepsis was considered present if the colony count from a central catheter lumen was > or = 5 times that of the peripheral blood. The incidence of catheter-related sepsis for single-lumen catheters was 2.6% (2 of 78) compared with 13.1% for triple-lumen catheters (13 of 99) (p < .01). No correlation was found with the number of insertion attempts, catheter days, or patient's age.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Martin Titanline arterial clamp. A new lightweight alternative

When haemostatic clamps are applied, evidence of injury at the site of clamp application may be seen when the clamp is removed. Rarely, the intima may be disrupted. When a new arterial clamp became available, a study was designed to compare the Martin Titanline arterial clamp (13-143-35, curved arterial clamp) with several other arterial clamps already in use. The Martin clamp is a modified pivot-point, preset-tension, spring-controlled arterial clamp. The closing pressures of several clamps were measured objectively. The injury produced when the clamps were applied to occlude the blood flow on the carotid artery of a dog was assessed by histological study of the excised segments of the arterial wall. Histological cross-sections were prepared from canine carotid artery which had been perfused for 1 h after the clamp had been applied for 1 h. Histological evidence of injury was limited to disruption of the intimal layer and compression of the medial layer. No significant difference between the amount of damage caused by the DeBakey, Satinsky or Martin clamp was identified. When compared to the other varieties of clamp listed above, the Martin clamp had a significantly lower closing pressure (304 g) compared with 580g (Bulldog), 580 g (Satinsky), and 686 g (DeBakey). The Martin clamp was easier to apply, did not obstruct the operative field as readily and had good clamp-retention characteristics throughout the procedure.     

Comparison of percutaneous endoscopic gastrostomy with Stamm gastrostomy.

In a review of 125 percutaneous endoscopic gastrostomies (PEG) and 88 Stamm gastrostomies performed at Duke University Medical Center since 1978, the average operating room time for PEG (50 +/- 20 min) was shorter than for Stamm (96 +/- 26 min) (p less than 0.0001). General anesthesia was administered in only 13% of PEG placements compared with 64% of Stamm gastrostomies. The cost of PEG was about $1000 less than for Stamm gastrostomies. The average time after surgery until use of the feeding tube was 1.8 days for PEG compared with 3.4 days for Stamm (p less than 0.0001). The overall complication rate after PEG was 8.8% (4.0% major) compared with 23.9% for Stamm gastrostomies (10.2% major) (p less than 0.005). PEG reduces operative time, necessity for general anesthesia, expense of insertion, incidence of complications, and requires less recovery time before use. PEG is the procedure of choice for gastric feeding access.     

Slow degeneration of zebrafish Rohon-Beard neurons during programmed cell death.

Rohon-Beard cells are large, mechanosensory neurons located in the dorsal spinal cord of anamniote vertebrates. In most species studied to date, these cells die during development. We followed labeled Rohon-Beard cells in living zebrafish embryos and found that they degenerate slowly, over many days. During degeneration, the soma shrinks and finally disappears, and the processes become beady in appearance and finally break apart, but they do not retract. Zebrafish Rohon-Beard cells apparently fragment their DNA, as revealed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) labeling, before undergoing degenerative morphologic changes. We also followed the development of labeled dorsal root ganglion neurons, as they are developing at the same stages that Rohon-Beard cells are degenerating. We found that, although axons of both cell types extend into similar regions, Rohon-Beard cells degenerate normally in mutants lacking dorsal root ganglia, providing evidence that interactions between the two cell types are not responsible for Rohon-Beard cell degeneration. Developmental Dynamics 229:30-41,2004.     

Influenza vaccination: a collaborative effort to improve the health of the community.

BACKGROUND: The need to improve influenza vaccination delivery in our community became painfully clear during the winter of 1997-1998 when high rates of respiratory illness led to congestion in the emergency department and a critical shortage of hospital beds. In response, the local hospital and the Department of Health launched a collaborative program to increase influenza vaccine coverage in the community. METHODS: The partnership was designed to increase the number of citizens receiving influenza vaccine and to moderate the severity of lower respiratory tract illness during the winter season. A variety of methods were used to increase public awareness, enhance vaccine delivery, and create a relatively seamless service for the community. RESULTS: During three seasons, influenza vaccination rates increased by a relative 150%. This represented immunization of 16% of the entire community and more than 75% of residents older than 65 years. Hospital employee vaccination rates also rose from 34% to 58%. When compared with other hospitals in the county, the campaign reduced the average number of annual visits to the emergency department for all respiratory diagnoses by 34% and exacerbations of chronic obstructive pulmonary disease by 46%. CONCLUSIONS: This influenza vaccination program illustrates the potential for synergy that exists between local departments of health and community hospitals in successfully increasing vaccine delivery to the community. Furthermore, it also suggests that such efforts can be successful in reducing use of the emergency department, resulting in a positive impact on the health of the community.     

Flow-induced cerebral vasodilatation in vivo involves activation of phosphatidylinositol-3 kinase, NADPH-oxidase, and nitric oxide synthase.

Reactive oxygen species (ROS) such as superoxide (O2*-) and hydrogen peroxide (H2O2) are known cerebral vasodilators. A major source of vascular ROS is the flavin-containing enzyme nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase. Activation of NADPH-oxidase leads to dilatation of the basilar artery in vivo via production of H2O2, but the endogenous stimuli for this unique vasodilator mechanism are unknown. Shear stress is known to activate both NADPH-oxidase and phosphatidylinositol-3 kinase (PI3-K) in cultured cells. Hence, this study used a cranial window preparation in anesthetized rats to investigate whether increased intraluminal blood flow could induce cerebral vasodilatation via the activation of NADPH-oxidase and/or PI3-K. Bilateral occlusion of the common carotid arteries to increase basilar artery blood flow caused reproducible, reversible vasodilatation. Topical treatment of the basilar artery with the NADPH-oxidase inhibitor diphenyleneiodonium (DPI) (0.5 and 5 micromol/L) inhibited flow-induced dilatation by up to 50% without affecting dilator responses to acetylcholine. Treatment with the H2O2 scavenger, catalase similarly attenuated flow-induced dilatation, suggesting a role for NADPH-oxidase-derived H2O2 in this response. The nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) partially reduced flow-induced dilatation, and combined treatment with a ROS inhibitor (DPI or catalase) and L-NAME caused a greater reduction in flow-induced dilatation than that seen with any of these inhibitors alone. Flow-induced dilatation was also markedly inhibited by the PI3-K inhibitor, wortmannin. Increased O2*- production in the endothelium of the basilar artery during acute increases in blood flow was confirmed using dihydroethidium. Thus, flow-induced cerebral vasodilatation in vivo involves production of ROS and nitric oxide, and is dependent on PI3-K activation.